OBJECTIVE: To determine the effect of probucol (PR) on fatty acid composition of plasma lipids in patients with hypertriglyceridemia during the fasting and postprandial states. DESIGN: Open-label, single-center, 6-week treatment, baseline-controlled trial. SETTING: Outpatient clinical research center. PATIENTS: Six patients with established hypertriglyceridemia and no complicating medical conditions. INTERVENTION: Step 1 American Heart Association diet and no lipid-lowering medications for at least 4 weeks. Lead to a baseline standarized meal ingestion with postprandial blood samplings. After 6 weeks of treatment with 500-mg of PR twice daily and diet, the meal tests were repeated. MEASUREMENTS: The clinical status, 3-day food records, postprandial blood samplings (0, 2, 4, 6, and 8 hours) for lipid and fatty acids in whole plasma, triglyceride (TG), phospholipid (PL), and cholesteryl ester (CE) fractions. RESULTS: PR had the following effects: (1) In plasma, cholesterol, high-density lipoprotein cholesterol, apolipoprotein (Apo) A1, and ApoB were decreased postprandially. ApoC111 ratio (heparin-treated plasma versus precipitate) was decreased in the fasting state. (2) The saturated/unsaturated (S/U) fatty acid ratios in the PL, TG, and CE fractions were elevated postprandially and increased in CE in the fasting state. In the PL fraction it was due to an increase in the percentage of myristic, palmitic, stearic, and oleic acids and a decrease in linolenic, eicosatrienoic, and arachidonic acids. In the TG and CE fractions the changes were not due to any particular patterns of fatty acids. The ratio of arachidonic/eicosatrienoic acid was decreased postprandially in PL and CE fractions. The ratio of eicosatrienoic/linoleic acid was decreased in PL and increased in CE fractions. (3) The S/U ratio in the lipoprotein (Lp) B and LP(a) lipid components decreased in PL and CE. Lp(a) was more saturated with respect to fatty acids than LpB. CONCLUSION: PR treatment for 6 weeks increased postprandial S/U fatty acid ratios. This was due to a combination of an increase in saturated and monounsaturated levels and a decrease in polyunsaturated levels. The effect was most notable in the PL fraction. In those systems dependent on the pattern of fatty acids, the fatty acid compositional change could modify biological responses in clinically important ways during lipid-lowering therapy. The change toward saturation of fatty acids in the postprandial state may contribute to the antioxidant properties of probucol.